Researchers find flu 'weak spot'

The 3D structure of the nucleoprotein of the flu virus

US researchers believe they have found a weak spot in the flu virus which if targeted could stop it in its tracks.

A 3D structure of a protein which helps the flu virus to replicate has shown that even minor changes to a small section stop it working.

The nucleoprotein is present in several types of flu including bird flu and normal seasonal strains.

The study in Nature offers a potential target for the development of new drugs to add to current antiviral treatments.

The influenza A nucleoprotein has a vital role in helping the flu virus to replicate by linking the RNA - or genetic information - into a structure which can be shipped out to infect other cells.

New antivirals are especially needed at the moment as some H5N1 viruses are resistant to Tamiflu Dr Yizhi Jane Tao

Single nucleoproteins join together into rings which then stack on top of each other into long columns.

By working out the 3D structure of the protein with X-ray crystallography, researchers at Rice University in Texas were able to ascertain that single mutations in part of the 'tail loop' of the protein were enough to stop it linking with another nucleoprotein.

If the nucleoprotein is unable to function because it can't link into the correct structure, the virus cannot replicate.

The researchers said the 'binding pocket' they identified in the tail loop of the protein was a potential target for the development of a new class of drugs to fight flu.

Antivirals

Current antivirals such as Tamiflu and Relenza belong to a class of drugs called neuraminidase inhibitors, which are designed specifically to target the influenza virus.

They work by stopping the virus sticking onto cells in the upper respiratory tract.

Governments around the world including in the UK have been stockpiling the drug in case of a pandemic but there have been reports of resistance to Tamiflu in people with bird flu.

Study leader Dr Yizhi Jane Tao said: "To first determine the status of the nucleoprotein we needed to obtain the structure of the molecule, which plays a role in genome packaging and release of the genome into the infected cell."

The nucleoprotein is made up of 500 amino acids - the building blocks of proteins - with about 30 amino acids in the tail loop.

"We found that one mutation in only one residue out of 30 was enough to prevent the nucleoproteins coming together to form the building blocks for the columns, and without those columns the virus cannot make copies and infect other cells," she added.

"New antivirals are especially needed at the moment as some H5N1 viruses are resistant to Tamiflu."

Flu expert Professor John Oxford, professor of virology at Queen Mary's School of Medicine and Dentistry, said the finding was "potentially hugely important".

"We desperately need a new class of drugs. It's another good target because the nucleoprotein is conserved across all the influenza A viruses so if you develop a drug against it, it could be active against all the influenza A viruses.

"With other self-replicating viruses like HIV it's been clear that if you treat people with several drugs it has more than an additive effect so even without the issue of resistance, the ability to treat people with two drugs would be very significant."